{"entity":{"id":"monarche","kind":"trial","name":"monarchE","aka":[],"tldr":"The first CDK4/6 inhibitor to reduce recurrence after surgery in high-risk hormone-positive breast cancer.","summary":"monarchE, trial NCT03155997 sponsored by Eli Lilly and reported in 2020, produced the first CDK4/6 inhibitor to reduce recurrence after surgery in high-risk, node-positive HR-positive, HER2-negative early breast cancer. It randomised 5,637 patients to two years of abemaciclib plus endocrine therapy or endocrine therapy alone, met its primary invasive disease-free survival endpoint at two years with the benefit widening at five years in a carry-over effect, and improved distant relapse-free survival, with overall survival trending favourably but not yet significant. OnCo links it to HR-positive breast cancer, abemaciclib, Stephen Johnston, Nadia Harbeck, Miguel Martín, the lymph node status term, the idea of using residual disease tests to decide who needs ten years of hormone therapy and the monarchE and NATALEE papers. Whether the benefit becomes a survival benefit is the open question.","status":"positive","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT03155997","url":"https://clinicaltrials.gov/study/NCT03155997"}],"tags":[],"related":[],"cancers":["breast-hr-positive","hr-positive-early-high-risk"],"sections":[],"technologies":["cdk46-inhibitor"],"targets":[],"drugs":["abemaciclib"],"companies":["eli-lilly"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["stephen-johnston","nadia-harbeck","miguel-martin"],"bottlenecks":[],"keyPapers":["paper-monarche-lancet-oncol-2023","paper-monarche-ann-oncol-2026-update"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03155997","phase":"3","setting":"Adjuvant abemaciclib 2 years + endocrine therapy in high-risk node-positive HR+/HER2- breast cancer","sponsor":"Eli Lilly","result":"iDFS HR 0.68.","started":"2017-07-12","startedType":"actual","yearReported":2020,"enrolled":5637,"enrolledBasis":"registry","outcomes":[{"endpoint":"Invasive disease-free survival at 2 years","primary":true,"unit":"%","arms":[{"name":"Abemaciclib + endocrine therapy","n":2808,"value":92.2},{"name":"Endocrine therapy alone","n":2829,"value":88.7}],"hr":0.75,"ci":[0.6,0.93],"p":"0.01","source":"https://ascopubs.org/doi/10.1200/JCO.20.02514"},{"endpoint":"Invasive disease-free survival at 5 years","unit":"%","arms":[{"name":"Abemaciclib + endocrine therapy","value":83.6},{"name":"Endocrine therapy alone","value":76}],"hr":0.68,"ci":[0.6,0.77],"source":"https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(23)00525-2/fulltext"},{"endpoint":"Distant relapse-free survival at 5 years","unit":"%","arms":[{"name":"Abemaciclib + endocrine therapy","value":86},{"name":"Endocrine therapy alone","value":79.2}],"hr":0.675,"source":"https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(23)00525-2/fulltext"}],"replication":"Confirmed by NATALEE (ribociclib) for the CDK4/6 adjuvant concept in high-risk disease; the benefit widened over time (carry-over effect)."},"route":"/trials/monarche/","neighbours":{"cancer":[{"id":"hr-positive-early-high-risk","kind":"cancer","name":"High-risk early HR-positive breast cancer","route":"/cancers/hr-positive-early-high-risk/"},{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"}],"technology":[{"id":"cdk46-inhibitor","kind":"technology","name":"CDK4/6 inhibitors","route":"/technologies/cdk46-inhibitor/"}],"drug":[{"id":"abemaciclib","kind":"drug","name":"Abemaciclib","route":"/drugs/abemaciclib/"}],"company":[{"id":"eli-lilly","kind":"company","name":"Eli Lilly (incl. Loxo)","route":"/companies/eli-lilly/"}],"person":[{"id":"miguel-martin","kind":"person","name":"Miguel Martín","route":"/people/miguel-martin/"},{"id":"nadia-harbeck","kind":"person","name":"Nadia Harbeck","route":"/people/nadia-harbeck/"},{"id":"stephen-johnston","kind":"person","name":"Stephen Johnston","route":"/people/stephen-johnston/"}],"paper":[{"id":"paper-monarche-lancet-oncol-2023","kind":"paper","name":"Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial","route":"/key-papers/paper-monarche-lancet-oncol-2023/"},{"id":"paper-monarche-jco-2020","kind":"paper","name":"monarchE: two years of abemaciclib after surgery in high-risk, hormone-receptor-positive early breast cancer","route":"/key-papers/paper-monarche-jco-2020/"},{"id":"paper-natalee-nejm-2024","kind":"paper","name":"NATALEE: three years of ribociclib after surgery in a broad population of hormone-receptor-positive early breast cancer","route":"/key-papers/paper-natalee-nejm-2024/"},{"id":"paper-monarche-ann-oncol-2026-update","kind":"paper","name":"Overall survival with abemaciclib in early breast cancer","route":"/key-papers/paper-monarche-ann-oncol-2026-update/"}],"term":[{"id":"efs","kind":"term","name":"Event-free / disease-free survival (EFS, DFS, iDFS, RFS)","route":"/terms/efs/"},{"id":"lymph-node-status","kind":"term","name":"Lymph node status (node-positive / node-negative)","route":"/terms/lymph-node-status/"},{"id":"surrogate-validation","kind":"term","name":"Surrogate endpoint validation: which stand-ins have earned trust","route":"/terms/surrogate-validation/"}],"idea":[{"id":"idea-bio2-mrd-guided-endocrine-duration","kind":"idea","name":"Use residual disease tests to decide who needs ten years of hormone therapy","route":"/ideas/idea-bio2-mrd-guided-endocrine-duration/"}],"roadmap":[{"id":"hormonal-therapy-roadmap","kind":"roadmap","name":"Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test","route":"/roadmaps/hormonal-therapy-roadmap/"}]}}